CRISPR: What It Is and Where Gene Editing Hits Its Ethical Limits

How CRISPR-Cas9 works

At the heart of it all is a simple pairing: a guide RNA and a protein that cuts. Researchers build a short synthetic RNA that matches an exact sequence in the DNA they want to change — creating an RNA sequence is far simpler than designing a custom protein from scratch. That guide RNA carries the Cas9 protein to the precise spot in the genome it’s aimed at, where Cas9 cuts both strands of the DNA. From that cut, scientists can get a deletion, or — by supplying an extra template — the insertion of a new sequence.

The system wasn’t invented in a lab out of thin air. CRISPR sequences were first spotted in bacteria back in the early 1990s: they’re part of the natural immune system these microorganisms use to recognize and destroy the viruses that attack them. Only later did scientists realize that the same recognize-and-cut mechanism could be adapted to work on the genome of other organisms, from yeast to mice to the human cell.

Somatic versus germline editing: the line that matters

CRISPR doesn’t always carry the same kind of consequence, and this is where most of the ethical debate plays out. The cells of the human body fall into two broad genetic families: somatic cells, which make up organs and tissue, and germline cells, the ones involved in reproduction and produced through meiosis. Editing the first stays a private matter for the treated person. Editing the second, or an embryo in its early stages, means writing a change that passes to children, and to their children in turn.

Real-world example: a gene therapy applied to the blood cells of a sick adult changes only those cells — the change stays with the patient and never touches their eggs or sperm. That’s somatic editing, categorically different from an intervention on an embryo, which would also affect that person’s descendants.

The He Jiankui case: when editing reached a human embryo

In November 2018, Chinese researcher He Jiankui went public, first through scientific press reports and then at the Second International Human Genome Editing Summit in Hong Kong, revealing that he had used CRISPR to edit the embryos that became twin girls, named Lulu and Nana. The stated goal was to make the girls resistant to HIV infection, by artificially reproducing a small deletion in the CCR5 gene that already gives some people this protection naturally.

The numbers behind the experiment, reconstructed by an academic analysis of the case, show just how immature the technique still was when applied to human embryos: of 31 embryos injected with CRISPR, 70% showed successful editing; of those, 13 were transferred for implantation in five women, resulting in two pregnancies. In at least one of the twins, the edit didn’t affect every cell uniformly, a phenomenon geneticists call mosaicism: the intended genetic change was present in only part of the body, not throughout.

The scientific community’s reaction was close to unanimous condemnation. Jennifer Doudna, one of the scientists who made CRISPR-Cas9 usable as an editing tool, has described feeling deeply unsettled by the news. Francis Collins, then director of the U.S. National Institutes of Health, called the experiment profoundly disturbing. Not every comment was outright condemnation: some defended the choice of target, HIV resistance, while sharply criticizing how it was pursued — among the most-cited problems were inadequate informed consent and the lack of real medical necessity, since effective, far less risky methods already exist to prevent HIV transmission from an HIV-positive father to an embryo. On the institutional side, Chinese authorities opened an official investigation on January 21, 2019, and SUSTC, the university where He Jiankui worked, dismissed him that same month.

Where bioethics committees actually stand

The He Jiankui case is often retold as proof that heritable editing is banned everywhere. The stance of bioethics committees is more nuanced. The Nuffield Council on Bioethics, a leading British body, published a report in July 2018 devoted specifically to gene editing applied to human reproduction, the result of a preliminary ethical review that had begun back in 2016.

The Nuffield Council holds that any heritable editing intervention must, above all, be intended for the welfare of the future person and stay consistent with that welfare; it also holds that it must not increase inequality, discrimination or division in society. On top of these principles come more practical conditions: that there has been a genuine opportunity for broad and inclusive public debate about the technique’s use, that further research has established standards of clinical safety, and that risks to individuals, groups and society as a whole have been properly assessed. If those conditions were met, the Council indicates the intervention should still be strictly regulated — in the United Kingdom, by the Human Fertilisation and Embryology Authority — introduced only within a monitored clinical study, and licensed on a case-by-case basis.

International governance and the equity question

Around the same time the He Jiankui case was breaking, the World Health Organization had already launched its own governance process: in December 2018, it set up a multidisciplinary expert committee tasked with global standards for overseeing human genome editing, with a mandate to examine somatic, germline and heritable editing as separate categories. The work concluded on July 12, 2021, with the publication of recommendations spanning nine distinct areas, including international registries for human genome editing, international research and medical travel, and — a point that lands differently in light of episodes like the one in Hong Kong, even though the document doesn’t name it — illegal, unregistered, unethical or unsafe research.

One issue the WHO raises clearly is equity of access: the risk, its 2021 statement notes, is that human genome editing ends up fueling more health inequity between and within countries, rather than reducing it. The recommendations are the result of a consultation lasting over two years, involving hundreds of participants — scientists, patient groups, faith leaders and representatives of indigenous peoples, among others. For now, the 2021 recommendations remain the most recent international framework for governing human genome editing.